Toxoplasma gondii-infected cells are resistant to multiple inducers of apoptosis.
Infection with certain intracellular pathogens, including viruses and bacteria, may induce host cell apoptosis. On the other hand, infection with some viruses inhibits apoptosis. Complex protozoan parasites, including Toxoplasma gondii and members of Plasmodium, Leishmania, and Microsporidia, are also obligate intracellular pathogens, yet relatively little is known regarding their subversion of host cell functions. We now report that cells infected with T. gondii are resistant to multiple inducers of apoptosis, including Fas-dependent and Fas-independent CTL-mediated cytotoxicity, IL-2 deprivation, gamma irradiation, UV irradiation, and the calcium ionophore beauvericin. Inhibition of such a broad array of apoptosis inducers suggests that a mechanism common to many, or perhaps all, apoptotic pathways is involved. The inhibitory activity requires live intracellular parasite and ongoing protein synthesis. Despite T. gondii-mediated inhibition of DNA fragmentation, infected cells can still be lysed by CTL.
Nash
P B
PB
Department of Medicine, University of Colorado Health Sciences Center, Denver 80220, USA. nashp@heska.com
Purner
M B
MB
Leon
R P
RP
Clarke
P
P
Duke
R C
RC
Curiel
T J
TJ
D000818:Animals; D000900:Anti-Bacterial Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology; D017209:Apoptosis / Q000276:immunology* / Q000528:radiation effects; D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic / Q000528:radiation effects; D003609:Dactinomycin / Q000494:pharmacology; D047630:Depsipeptides; D005720:Gamma Rays; D006801:Humans; D007113:Immunity, Innate / Q000528:radiation effects; D007376:Interleukin-2 / Q000494:pharmacology / Q000528:radiation effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D010455:Peptides; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000469:parasitology / Q000528:radiation effects; D014122:Toxoplasma / Q000187:drug effects / Q000254:growth & development / Q000276:immunology* / Q000528:radiation effects; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays
D000900:Anti-Bacterial Agents; D047630:Depsipeptides; D007376:Interleukin-2; D010455:Peptides; D003609:Dactinomycin; C004456:beauvericin; D003513:Cycloheximide